Implementation of First-trimester Screening and Prevention of Preeclampsia: a Stepped Wedge Cluster-randomized Trial in Asia.

BACKGROUND: This trial aimed to assess the efficacy, acceptability and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia (PE) in Asia. METHODS: Between 1st August 2019 and 28th February 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from ten regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular six-week intervals, one cluster was randomized to transit from non-intervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm PE using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm PE ≥ 1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. RESULTS: Overall, 88.04% (42,897/48,725) of women agreed to undergo first-trimester screening for preterm PE. Among those identified as high-risk in the intervention phase, 82.39% (2,919/3,543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm PE between the intervention and non-intervention phases (adjusted odds ratio [aOR] 1.59; 95% confidence interval [CI] 0.91 to 2.77). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm PE (aOR 0.59; 95%CI 0.37 to 0.92). Additionally, it correlated with 54%, 55% and 64% reduction in the incidence of PE with delivery at <34 weeks (aOR 0.46; 95%CI 0.23 to 0.93), spontaneous preterm birth <34 weeks (aOR 0.45; 95%CI 0.22 to 0.92) and perinatal death (aOR 0.34; 95%CI 0.12 to 0.91), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events. CONCLUSIONS: The implementation of the screen-and-prevent strategy for preterm PE is not associated with a significant reduction in the incidence of preterm PE. However, low-dose aspirin effectively reduces the incidence of preterm PE by 41% among high-risk women. The screen-and-prevent strategy for preterm PE is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm PE on a global scale.

Fetal hemodynamic changes and mitochondrial dysfunction in myocardium and brain tissues in response to anemia: a lesson from hemoglobin Bart's disease.

OBJECTIVE: Whether or not the effects of anemia in the early phase, while the fetuses attempts to increase cardiac output to meet oxygen requirement in peripheral organs, is detrimental to the fetal developing vital organs is little-known. The objective of this is to compare prenatal cardiovascular changes and post-abortal cellular damages in the myocardium as a pumping organ and the brain as a perfused organ between anemic fetuses (using fetal Hb Bart's disease as a study model) in pre-hydropic phase and non-anemic fetuses. METHODS: Fetuses affected by Hb Bart's disease and non-anemic fetuses at 16-22 weeks were recruited to undergo comprehensive fetal echocardiography. Cord blood analysis was used to confirm the definite diagnosis of fetal Hb Bart's disease and normal fetuses. Fetal cardiac and brain tissues were collected shortly after pregnancy termination for the determination of oxidative stress and mitochondrial function, including mitochondrial ROS production and mitochondrial membrane changes. RESULTS: A total of 18 fetuses affected by Hb Bart's disease and 13 non-anemic fetuses were recruited. The clinical characteristics of both groups were comparable. The affected fetuses showed a significant increase in cardiac dimensions, cardiac function, cardiac output and brain circulation without deteriorating cardiac contractility and preload. However, in the affected fetuses, mitochondrial dysfunction was clearly demonstrated in brain tissues and in the myocardium, as indicated by a significant increase in the membrane potential change (p-value < 0.001), and a significant increase in ROS production in brain tissues, with a trend to increase in myocardium. The findings indicated cellular damage in spite of good clinical compensation. CONCLUSION: The new insight is that, in response to fetal anemia, fetal heart increases in size (dilatation) and function to increase cardiac output and blood flow velocity to provide adequate tissue perfusion, especially brain circulation. However, the myocardium and brain showed a significant increase in mitochondrial dysfunction, suggesting cellular damage secondary to anemic hypoxia. The compensatory increase in circulation could not completely prevent subtle brain and heart damage.

Fetal Cardiac Inflow Characteristics in Response to Fetal Anemia: Based on Fetal Hemoglobin Bart's Disease at Mid-Pregnancy.

OBJECTIVES: To identify the inflow (filling time fraction [FTF] and E/A ratio) characteristics of fetuses with anemia, and to evaluate the performance of the inflow markers in predicting the affected fetuses. METHODS: Fetuses at risk of hemoglobin (Hb) Bart's disease at 17-22 weeks were prospectively recruited to undergo echocardiography before diagnostic cordocentesis. Cardiac Doppler images were digitally stored for off-line blinded measurements of FTF and E/A ratio. RESULTS: A total of 428 fetuses at risk of Hb Bart's disease were analyzed, including 88 affected fetuses (20.6%). The mean gestational age at the time of diagnosis was 19.43 ± 1.5 weeks. The FTFs in both sides were significantly lower in the affected fetuses, whereas the E/A ratios of both sides were significantly higher in the affected group. According to the receiver operating characteristic curves, the performance of the FTF of the right side in predicting affected fetuses was slightly better than that of the left side (area under curve: 0.707 versus 0.680, P < .001). Likewise, the performance of the E/A ratio of the tricuspid valve was slightly better than that of the mitral valve. Also, FTF was superior to E/A ratio in predicting the affected fetuses. CONCLUSIONS: New insights leading to a better understanding of the fetal cardiac response to anemia are: 1) the FTFs in both sides were significantly decreased, suggesting some degree of diastolic ventricular dysfunction; 2) the E/A ratios of both sides were significantly increased, indicating volume load; and 3) The inflow parameters may be useful as a new predictor of fetal anemia, especially among pregnancies at risk.

Fetal Hemodynamic Response to Anemia in Early Gestation: Using Hemoglobin Bart's Disease as a Study Model.

OBJECTIVE: To assess fetal hemodynamic changes in response to anemia in early gestation, using fetal Hb Bart's disease as a study model. METHODS: A prospective study was conducted on pregnancies at risk for fetal Hb Bart's disease at 12-14 weeks of gestation. Fetal hemodynamics were comprehensively assessed by 2D ultrasound, Doppler velocity, and cardio-STIC just prior to the invasive procedure for diagnosis. The various hemodynamic parameters of the affected and unaffected fetuses were compared. RESULTS: Of 56 fetuses at risk, 17 had Hb Bart's disease and 39 were unaffected. The right and combined ventricular cardiac outputs (CO) were significantly higher in the affected fetuses (0.993 vs. 1.358; p < 0.001 and 1.010 vs. 1.236; p < 0.001, respectively), whereas the left CO tended to be higher but not significantly (1.027 vs. 1.113; p = 0.058). Cardiac dimensions, middle-cerebral artery peak systolic velocity, Tei index, and isovolemic contraction time were significantly increased, while the global sphericity index was significantly decreased. Interestingly, cardiac preload, ventricular wall thickness, shortening fraction, isovolemic relaxation time, and fetal heart rate were unchanged. Four fetuses had hydropic changes, but all cardiac functions were normal. CONCLUSION: Fetal anemia induces hypervolemia and increases cardiac output to meet the tissue oxygen requirement, resulting in an increase in size without hypertrophy, volume load without pressure load, and a decrease in the globular sphericity index. The heart works very well but works harder, especially systolic ventricular load. Hydrops fetalis due to anemia appears not to be caused by heart failure as previously believed but rather by volume load with high vascular permeability at least in early pregnancy.

Placenta-Derived Extracellular Vesicles in Pregnancy Complications and Prospects on a Liquid Biopsy for Hemoglobin Bart's Disease.

Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original cells and tissues, including the placenta. Placenta-derived EVs can be detected in maternal circulation at as early as six weeks of gestation, and their release can be triggered by the oxygen level and glucose concentration. Placental-associated complications such as preeclampsia, fetal growth restriction, and gestational diabetes have alterations in placenta-derived EVs in maternal plasma, and this can be used as a liquid biopsy for the diagnosis, prediction, and monitoring of such pregnancy complications. Alpha-thalassemia major ("homozygous alpha-thalassemia-1") or hemoglobin Bart's disease is the most severe form of thalassemia disease, and this condition is lethal for the fetus. Women with Bart's hydrops fetalis demonstrate signs of placental hypoxia and placentomegaly, thereby placenta-derived EVs provide an opportunity for a non-invasive liquid biopsy of this lethal condition. In this article, we introduced clinical features and current diagnostic markers of Bart's hydrops fetalis, extensively summarize the characteristics and biology of placenta-derived EVs, and discuss the challenges and opportunities of placenta-derived EVs as part of diagnostic tests for placental complications focusing on Bart's hydrop fetalis.

Outcomes of pregnancies complicated by haemoglobin H-constant spring and deletional haemoglobin H disease: A retrospective cohort study.

The objective of the study was to compare the maternal and foetal outcomes of pregnancies complicated by Hb H-constant spring (HbH-CS) disease/deletional HbH (HbH-del) disease and low-risk pregnancies. A retrospective cohort research was undertaken on singleton pregnancies with Hb H-CS and Hb H-del diseases. The controls were randomly selected with a control-to-case ratio of 10:1. A total of 55 cases of HbH-CS disease, 231 cases of HbH-del disease and 2860 controls were compared. The mean gestational age at delivery and birthweight were significantly lower in the HbH-CS group than in the HbH-del and control groups. The clinical course of Hb H-CS was more severe than that of HbH-del disease. The rates of preterm birth, foetal growth restriction and low birthweight were significantly increased in the HbH-CS and Hb H-del groups. These rates were significantly greater in the HbH-CS group than in the H-del group. The maternal outcomes were not significantly different among the three groups. In conclusion, pregnancy worsens the course of HbH disease, more noticeably in HbH-CS disease. Hb H disease significantly increases the risk of adverse foetal outcomes, more noticeably in the HbH-CS group. Pregnancy is relatively safe for women with HbH disease.

Reference Intervals of Fetal Cardiac Volume Between 14 and 40 Weeks of Gestation.

OBJECTIVES: To construct the reference intervals for the cardiac volume (CV) of normal fetuses between 14 and 40 weeks of pregnancy. METHODS: Low risk singleton pregnancies with normal fetuses were prospectively recruited to acquire 4D-cardio-spatiotemporal image correlation volume datasets (VDS). Subsequent off-line analyses of VDS were anonymously performed to calculate CV using the Virtual Organ Computer-aided AnaLysis technique. The reference intervals were established as a function of gestational age (GA), biparietal diameter (BPD), head circumference (HC), and estimated fetal weight (EFW) based on the best-fitted models for both mean and standard deviation (SD). RESULTS: A total of 668 VDS were successfully calculated for CV. The best-fitted models for the means and SDs are as follow: 1) GA in week = 6.422 + e(-100.653 × GA) (SD = 0.641 - (0.170 × GA) + (0.009 × GA2 )). 2) BPD = 0.016 × (BPD)3.589 (SD = 2.663 - (1.410 × BPD) + (0.224 × BPD2 )). 3) HC = 0.00017 × (HC)3.537 (SD = 2.341 - (0.341 × HC) + (0.015 × HC2 )). The CV progressively increased with advancing fetal age (GA) and size (BPD, HC). CONCLUSIONS: The reference intervals of CV, theoretically best representing cardiac size, in relation to GA, BPD, HC, and EFW were first established and Z-score was readily calculated. These will be helpful in detection of cardiac abnormalities, especially those associated with cardiomegaly.

Hydrops Fetalis Associated with Fetal Hemoglobin H-Pakse Disease.

INTRODUCTION: Hemoglobin H-Pakse (Hb H-PS) disease is a variant of non-deletional Hb H disease associated with various degrees of anemia. The disorder is rare but commonly seen in Southeast Asia. However, the prenatal course of Hb H-PS disease has never been published. The objective of this report was to describe prenatal diagnosis and management of Hb H-PS disease, which is theoretically much more critical in fetal life than adult life. CASE PRESENTATION: The prenatal courses of two fetuses affected by Hb H-PS were comprehensively explored. Both of them showed sonographic signs of fetal anemia at 19-20 weeks of gestation (increased cardiac size and increase middle cerebral artery peak systolic velocity [MCA-PSV]). On follow-up scans, both revealed frank hydropic signs at 22-24 weeks. One fetus died at 24 weeks, shortly before the scheduled intrauterine blood transfusion (IUT). The other one underwent IUT at 22 weeks, leading to completely reversed hydropic signs, which resulted in successful outcomes that ended with the delivery of a healthy baby at term. The fetus needed only one IUT, and the course of anemic status improved in late pregnancy. IUT in this case was possibly beneficial to adult life. CONCLUSION: Fetuses with Hb H-PS may be associated with hydrops fetalis, usually occurring at mid-pregnancy. The hydrops tends to improve in late gestation. If they can pass through this most critical period in utero without anemic insults in developing organs, good long-term prognosis can be expected. This successful prenatal diagnosis and intrauterine treatment may encourage care providers to pay more attention to fetal Hb H-PS disease, to prevent anemic hypoxia in developing organs and adult diseases of fetal origin.

Fetal Hemodynamic Responses to Arterial Occlusion of Acardiac Twins.

The objective of this study was to comprehensively assess fetal hemodynamic adaptions to occlusive procedures. Twin pregnancies complicated with acardiac twin and hydrops fetalis of the pump twin were recruited. The occlusive procedures - either alcoholization, radiofrequency ablation, coil embolization or occlusive glue - were performed under ultrasound guidance. Various hemodynamic parameters were assessed before, shortly after, then every 6 h for 48 h and 2-4 weeks after the procedures. Seven pregnancies were recruited. The median (range) gestational age of intervention was 21 (17-26) weeks of gestation. Before the procedures, all cases showed normal cardiac function. Just after the procedures, all cases showed an increase in Tei index and isovolumic relaxation time but returned to preocclusion levels within 6-48 h, except for two cases that were persistently high. Increased preload and poor shortening fraction were observed in two cases, leading to heart failure, with one recovery and one death in utero. Five out of the seven cases got through the critical period with a gradual return to normal hemodynamics, ending with the disappearance of hydrops and successful outcomes. It was concluded that the occlusive procedure could aggravate the overworked heart, leading to heart failure. Preocclusion preload index and Tei index may predict risk of heart failure due to the occlusion. This small series strongly suggests that the occlusion should be performed before the deterioration of cardiac function.

Ultrasound Features of Fetal Anemia Lessons From Hemoglobin Bart Disease.

Insights gained from this review are as follows: (1) Ultrasound is highly effective in early detection of fetal hemoglobin (Hb) Bart disease. (2) The most sensitive parameters in predicting Hb Bart anemia appear to be the cardiac diameter-to-thoracic diameter ratio, middle cerebral artery peak systolic velocity, and placental thickness. (3) Several other ultrasound markers are helpful in increasing specificity, such as hepatosplenomegaly. (4) Hydrops fetalis is not a consequence of heart failure but rather of hypervolemia and high vascular permeability of fetuses, whereas heart failure is a very late consequence of a long-standing overworked heart. (5) Management guidelines for fetuses at risk of Hb Bart disease are proposed.

Comparison of pregnancy outcomes after second trimester amniocentesis between procedures performed by experts and non-experts.

OBJECTIVES: To compare the rate of fetal loss in pregnancy after second trimester amniocentesis between procedures performed by experts and non-experts and to assess other pregnancy complications as secondary outcomes. METHODS: A retrospective cohort study was performed on singleton pregnancies that underwent mid-trimester amniocenteses in a single institution. The fetal loss rates of procedures performed by experts and non-experts were collected and analyzed. Other adverse pregnancy outcomes were also examined. RESULTS: In total, 14,450 amniocenteses were performed during the study period. These included 11,357 (78.6%) procedures in the group expert operators and 3,093 (21.4%) procedures in the group non-expert operators. In the non-expert group, the fetal loss rate was slightly increased but not significantly (p=0.24).In addition, the higher number of spontaneous abortions was associated with blood-stained amniotic fluid sample (p<0.001; RR=9.28). Multiple needle insertions also increased in the non-expert group significantly. However, no difference in pregnancy outcomes was found between in single and multiple needle insertions. CONCLUSIONS: The amniocentesis procedures performed by the non-experts was not increase the fetal loss rate. However, the other adverse pregnancy outcomes, including preterm birth, low birth weight and fetal growth restriction were significantly increased in the non-expert group.

Comparison of the Performances of Middle Cerebral Artery Peak Systolic Velocity and Cardiothoracic Diameter Ratio in Predicting Fetal Anemia: Using Fetal Hemoglobin Bart's Disease as a Study Model.

OBJECTIVE: The aim of the study was to compare the performances of cardiothoracic diameter ratio (CTR) and middle cerebral artery peak systolic velocity (MCA-PSV) in predicting fetal hemoglobin (Hb) Bart's disease and identify the best CTR cut-off for each gestational period. METHODS: Pregnancies at risk of fetal Hb Bart's disease (gestational ages of 12-36 weeks) were prospectively recruited to undergo ultrasound examination. The measurements of CTR and MCA-PSV were performed and recorded before invasive diagnosis. RESULTS: During the study period (2005-2019), a total of 1,717 pregnancies at risk of fetal Hb Bart's disease met the inclusion criteria and were available for analysis, including 329 (19.2%) fetuses with Hb Bart's disease. The mean gestational age at the time of diagnosis was 19.30 ± 5.6 weeks, ranging from 12 to 36 weeks. The overall performance of CTR Z-scores is superior to that of MCA-PSV multiple of median (MoM) values; area under curve of 0.866 versus 0.711, p value <0.001. The diagnostic indices of CTR and MCA-PSV are increased with gestational age. Based on receiver operating characteristic curves of CTR Z-scores, the best cut-off points of CTR at 12-14, 15-17, 18-20, 21-23, and ≥24 weeks are 0.48, 0.49, 0.50, 0.51, and 0.54, respectively. The best cut-off of MCA-PSV is 1.3 MoM, giving the best performance at 21-23 weeks with a sensitivity of 91.8% and specificity of 85.5%. CONCLUSION: The performance of CTR is much better than MCA-PSV in predicting fetal anemia caused by Hb Bart's disease. Nevertheless, whether this can be reproduced in anemia due to other causes, like isoimmunization, is yet to be explored.

Fetal hydrometrocolpos with pre-axial mirror polydactyly as a new variant of McKusick-Kaufman syndrome.

This report describes a variant of McKusick-Kaufman syndrome presenting with a large fetal abdominal cyst of hydrometrocolpos at 37 weeks of gestation. The diagnosis was based on the ultrasound findings of a large homogeneous hypoechoic cyst (diameter of >10 cm) with incomplete septum, thickened wall, superiorly connecting to the dilated uterus, consistent with hydrometrocolpos. Additionally, pre-axial mirror polydactyly of the left foot was suspected. Postnatal examination/work-up confirmed the prenatal findings. This is the first report of prenatal diagnosis of hydrometrocolpos with complex polydactyly of mirror image pre-axial duplications containing nine toes instead of six-toe postaxial polydactyly.

Effectiveness of placental volume measured by virtual organ computer-aided analysis in prediction of fetal hemoglobin Bart's disease in late first trimester.

OBJECTIVE: To evaluate the effectiveness of placental volume measured by virtual organ computer-aided analysis (VOCAL) at 12 to 14 weeks of gestation in predicting fetal hemoglobin (Hb) Bart's disease among pregnancies at risk. METHODS: This study involves 3-dimensional ultrasound (3D-US) volume datasets derived from pregnancies at risk of fetal Hb Bart's disease at 12 to 14 weeks of pregnancy. VOCAL technique was used to measure and calculate placental volume by the authors, who did not know the fetal diagnosis. Placental thickness was also measured. The diagnostic values of placental volume and placental thickness in prediction of fetal Hb Bart's disease were calculated. RESULTS: Sixty-five volume datasets, including 22 datasets of the affected fetuses and 43 unaffected fetuses, were included. The mean placental volume (±SD) of the affected cases was significantly higher than that of the unaffected ones, 85.35 ± 20.84 cm3 vs 52.24 ± 19.01 cm3 (Student's t test, P < .001). In predicting Hb Bart's disease, placental volume and placental thickness had sensitivities of 77.3% and 72.7% respectively as well as specificities of 88.37% and 76.7% respectively. CONCLUSION: Of fetuses at risk of Hb Bart's disease, 3D-US VOCAL placental volume may be useful in early detection of affected fetuses. Its effectiveness is superior to that of conventional placental thickness measurement.

Comparisons of pregnancy outcomes between twin pregnancies with and without second-trimester amniocentesis.

OBJECTIVE: To assess the amniocentesis-related pregnancy loss rate and preterm birth rate among twin pregnancies undergoing amniocentesis. METHODS: A retrospective cohort study was conducted at a tertiary center. The study group included twin pregnancies undergoing amniocentesis during 16 to 22 weeks of gestation. The control group was those not undergoing amniocentesis. All amniocenteses were performed by the MFM specialists. The main outcomes were the rate of pregnancy loss (before 24 weeks) and preterm birth. RESULTS: A total of 332 cases in the study group and 1188 controls were analyzed. The percentages of maternal age ≥35 years, high parity, and cases complicated with medical diseases were significantly higher in the study group. The pregnancy loss rate after the procedure tended to be higher, but not significant, in the study group (3.0% vs 2.2% P = .383). Likewise, the rate of preterm birth in the study group was higher, but not significant (70.5% vs 66.0% P = .130). Logistic regression analysis to adjust confounding factors showed no significance of amniocentesis on pregnancy loss and preterm birth. CONCLUSION: Though amniocentesis in twin pregnancies has theoretical risk of pregnancy loss, it is relatively safe when performed by maternal-fetal medicine specialists. This information is useful for counseling, especially when performed by experienced hands.

Z Score Reference Ranges of Fetal Cardiac Output From 12 to 40 Weeks of Pregnancy.

OBJECTIVES: To develop the Z score reference ranges of fetal cardiac output (CO) in healthy fetuses from 12 to 40 weeks of pregnancy. METHODS: A cross-sectional descriptive study was undertaken among low-risk singleton pregnancies with healthy fetuses between 12 and 40 weeks. The right ventricular cardiac output (RCO), left ventricular cardiac output (LCO), and combined cardiac output (CCO) were measured by 2-dimensional ultrasound with the Doppler velocity of the aorta and pulmonary arteries. The pregnancies were followed until delivery RESULTS: The RCO, LCO, and CCO were determined in 700 fetuses. The predictive models of the CO as a function of gestational age (GA) and biparietal diameter were identified, and the Z score reference ranges were constructed. The means and standard deviations of CO on both sides were increased with GA and biparietal diameter as power models. Nomograms for the LCO, RCO, and CCO were established (ie, RCO = 0.000148 × GA4.283034 ; SD = 0.000131 × GA4.026209 ; LCO = 0.000514 × GA3.790944 ; SD = 0.000169 × GA3.815546 ). The RCO was much more increased than the LCO with advancing GA. CONCLUSIONS: The Z score reference ranges and percentile charts of fetal CO were constructed throughout gestation with a large sample size. This may be helpful in detection of cardiac disorders, especially cardiomyopathy, cardiac anomalies, fetal anemia, and fetal growth restriction.

Fetal Cardiac Remodeling in Response to Anemia: Using Hemoglobin Bart's Disease as a Study Model.

OBJECTIVE: To assess fetal cardiac remodeling in response to anemia, by comparing the fetal cardiac dimensions and global sphericity index (GSI) of normal fetuses and fetuses with anemia using fetal Hb Bart's disease as a study model. METHODS: Fetuses at risk for Hb Bart's disease undergoing cordocentesis at 18 to 22 weeks of gestation were recruited. Fetal cardiac dimensions including GSI (cardiac length to cardiac width ratio), interventricular septum thickness (IVST), left ventricular wall thickness (LVWT) and right ventricular wall thickness (RVWT) were measured. RESULTS: 215 pregnancies at risk met the inclusion criteria, including 54 affected fetuses and 161 normal fetuses. The mean GSI was significantly lower in the affected group (1.11 ±â€Š0.06 vs. 1.26 ±â€Š0.09, p-value 0.017). The GSI of the normal group was relatively constant regardless of gestational age. The IVST and LVWT tended to increase, but not significantly, in the affected group, whereas the RVWT was minimally but significantly increased. The ROC curve for GSI had an area under curve of 0.844. The best cut-off of GSI was 1.17, giving a sensitivity of 74.1 % and a specificity of 88.2 %. CONCLUSION: Fetal cardiac remodeling in response to anemia causes a marked decrease in global GSI with minimal hypertrophy as an adaption to volume overload. Importantly, GSI is a new maker for anemia and may play a role in clinical application for early detection of fetal anemia, possibly due to any cause. Additionally, GSI measurement is simple and gestational age-independent.

The best cutoff value of middle cerebral artery peak systolic velocity for the diagnosis of fetal homozygous alpha thalassemia-1 disease.

OBJECTIVE: To determine the best cutoff value of middle cerebral artery peak systolic velocity (MCA-PSV) for the diagnosis of fetuses with homozygous alpha thalassemia-1 disease. METHODS: Pregnancies at risk for fetal homozygous alpha thalassemia-1 disease at 18 to 22 weeks were recruited. MCA-PSV was measured before cordocentesis for hemoglobin typing and complete blood count. The performance of the MCA-PSV for identifying affected fetuses was evaluated using a best cutoff value derived from the receiver operating characteristic (ROC) curve. RESULTS: Among 142 fetuses at risk, 46 (32.4%) fetuses were diagnosed as affected by homozygous alpha thalassemia-1 disease and were categorized as mild anemia (16.3%), moderate anemia (58.1%), and severe anemia (25.6%). With the best cutoff point of MCA-PSV > 1.30 multiples of the median (MoM) or >30.0 cm/s, the sensitivity for predicting fetal homozygous alpha thalassemia-1 was 100%. CONCLUSIONS: MCA-PSV > 1.30 MoM is the best cutoff value for the diagnosis of all degrees of fetal anemia from homozygous alpha thalassemia-1 fetuses. Because of its simplicity for interpretation and high efficacy, a cutoff value of MCA-PSV > 30 cm/s can also be used as an alternative marker for fetal anemia screening during 18 to 22 weeks of gestation.

Fetal Down syndrome screening models for developing countries; Part I: Performance of Maternal Serum Screening.

BACKGROUND: To identify the performance of fetal Down syndrome (DS) screening for developing countries. METHODS: A prospective study on MSS (maternal serum screening) with complete follow-ups (n = 41,924) was conducted in 32 network hospitals in the northern part of Thailand. Various models of MSS were tested for performance. RESULTS: MSS based on Caucasian reference range resulted in very high false positive rate (FPR; 13%) in our country, compared to the rate of 7.8% with our own (Thai) reference range, whereas the detection rate was comparable. As individual screening, C-S (contingent first trimester screening including PAPP-A, and free beta-hCG, classified as a) high risk [> 1:30], indicated for invasive diagnosis; b) intermediate risk [1:30-1500], indicated for STS; and c) low risk [< 1:1500], need no further tests.) was the most effective model (sensitivity 84.9%, FPR 7.7%) but nearly one-third needed the second trimester test (STS) because of intermediate results. Additionally, about one-third had their first visits in the second trimester and had no chance of FTS (first trimester screening). C-S plus STS had a sensitivity of 82.4% and FPR 8.1% whereas independent first and second trimester screening model (I-S) gave the sensitivity of 78.4% and FPR of 7.5% but was much more convenient and practical. CONCLUSION: C-S plus STS was the most effective models while I-S model was also effective and may be better for developing countries because of its simplicity and feasibility.

Z Score Reference Ranges of Fetal Cardiothoracic Diameter Ratio.

OBJECTIVE: This study aims to establish the z score reference ranges of cardiothoracic diameter ratio (CTR) of normal fetuses from 14 to 40 weeks' gestation. METHOD: A cross-sectional study was conducted on low-risk singleton pregnancies with healthy fetuses. The CTR was performed using simple 2-dimensional sonography on the typical fetal 4-chamber view. The reference ranges were constructed according to gestational age (GA), biparietal diameter (BPD), and head circumference (HC) as independent variables based on the best-fit models, both mean and standard deviation (SD). RESULTS: A total of 683 fetuses were measured for CTR. The best-fit equations for the mean and SD as a function of GA, BPD, and HC are as follows: (1) CTR = 0.365 + 0.004 × GA in weeks (SD = 0.031 + 0.001 × GA); (2) CTR = 0.373 + 0.014 × BPD in cm (SD = 0.034 + 0.004 × BPD); and (3) CTR = 0.373 + 0.004 × HC in cm (SD = 0.032 + 0.001 × HC). The CTR was slightly increased with advanced GA, BPD, and HC. CONCLUSION: Complete nomograms with z score reference ranges of CTR were established throughout pregnancy. These nomograms may be useful to detect cardiac abnormalities.